Validation of differential methylation at specific loci in adipose tissue before and after gastric bypass and the major weight loss associated with it

D Macartney-Coxson*, M Benton, A Johnstone and R S Stubbs

Objective: Type-2 diabetes and obesity are diseases of epidemic proportions.

Gastric bypass surgery results in major weight-loss and in many cases substantial  amelioration of insulin resistance and type-2 diabetes. Using gastric bypass as a model system we have identified differentially methylated loci in adipose tissue before and after surgery. We wish to validate a number of these loci as a first step towards understanding their significance in disease.

Background: We previously investigated DNA methylation, in two different adipose tissues subcutaneous adipose and omentum before and after gastric bypass and associated weight-loss using the high-density Illumina 450K platform. A paired analyses before surgery andafter subsequent weight-loss revealed significant differential methylation (Bonferroni p<1x10-7) in subcutaneous adipose and omentum at 3601 and 15 cytosine guanine dinucleotides (CpGs) respectively. This differential methylation was observed within obesity candidate genes, genomic regions associated with obesity, non-coding RNA loci and genes involved in epigenetic regulation and development. We sought WMRF funding to validate a number of these differentially methylated loci using an independent technique, pyrosequencing.